Small molecule that stabilizes CHI3L1–Gal3BP shifts glioblastoma macrophages and adds to anti-PD-1
- A screen found LZ6, which strengthens CHI3L1 binding to Gal3BP and reduces galectin-3 engagement in vitro.
- It pushed macrophages toward an anti-tumor state in patient-derived glioblastoma cultures and orthotopic GL261 tumors.
- Oral dosing extended survival in mice, and more so alongside anti-PD-1.
💡 Points Based on the abstract
Stabilizing a protein complex rather than blocking it is an unusual pharmacological idea, and the oral survival benefit in an orthotopic model is the interesting part. But GL261 is a notoriously immunogenic mouse line that flatters checkpoint combinations, and glioblastoma has repeatedly failed to follow it. I'd need brain exposure and target engagement data before taking the mechanism seriously.